Spatially Inhomogeneous Superconducting State near Hc2H_{\rm c2} in UPd2_2Al3_3

We have performed $^{27}$Al-NMR measurements on single-crystalline UPd$_2$Al$_3$ with the field parallel to the $c$ axis to investigate the superconducting (SC) properties near the upper critical field of superconductivity $H_{\rm c2}$. The broadening of the NMR linewidth below 14~K indicates the appearance of the internal field at the Al site, which originates from the antiferromagnetically ordered moments of U 5$f$ electrons. In the SC state well below $\mu_0H_{\rm c2}$ = 3.4~T, the broadening of the NMR linewidth due to the SC diamagnetism and a decrease in the Knight shift are observed, which are well-understood by the framework of spin-singlet superconductivity. In contrast, the Knight shift does not change below $T_{\rm c}(H)$, and the NMR spectrum is broadened symmetrically in the SC state in the field range of 3~T $< \mu_0 H < \mu_0 H_{\rm c2}$. The unusual NMR spectrum near $H_{\rm c2}$ suggests that a spatially inhomogeneous SC state such as the Fulde-Ferrell-Larkin-Ovchinnikov (FFLO) state would be realized.Comment: 5 pages, 5 figure

The Early Decline of alpha-Fetoprotein and Des-gamma-Carboxy Prothrombin Predicts the Response of Hepatic Arterial Infusion Chemotherapy in Hepatocellular Carcinoma Patients

Introduction: Molecular targeting drugs are recommended as second-line treatment for intrahepatic advanced hepatocellular carcinoma (HCC). However, in Asia, hepatic arterial infusion chemotherapy (HAIC) is also considered as a second-line treatment because it improves the survival of responders. The aim of this study was to predict responders and non-responders to HAIC with low-dose cisplatin plus 5-fluorouracil (LFP) using tumor markers. Objective and Methods: The data of 47 patients who received LFP for the first time in our hospital were analyzed retrospectively. We evaluated the association between treatment response by Response Evaluation Criteria in Solid Tumors and the changing ratio of the serum concentration of alpha-fetoprotein (AFP),Lens culinarisagglutinin-reactive fraction of AFP (AFP-L3), and des-gamma-carboxy prothrombin (DCP) 2 weeks after LFP initiation. Results: The number of patients showing a complete response (CR), a partial response (PR), stable disease (SD), and progressive disease (PD) was 0 (0%), 20 (43%), 18 (38%), and 9 (19%), respectively. The AFP ratio showed significant positive correlations for PR vs. SD (p= 0.004) and PR vs. PD (p= 0.003). The DCP ratio correlated significantly for PR vs. SD (p= 0.02). The optimal cutoff values for responders were 0.79 for the AFP ratio and 0.53 for the DCP ratio. Prediction using both or either cutoff value showed 93% sensitivity, 53% specificity, a 94% negative predictive value, and a 57% positive predictive value. Conclusion: Optimal cutoff values for AFP and DCP ratios enable prediction of nonresponders to HAIC with LFP. This simple and early assessment method allows the use of HAIC and molecular targeting drugs for HCC treatment

Dynamic stability during level walking and obstacle crossing in children aged 2–5 years estimated by marker-less motion capture

In the present study, dynamic stability during level walking and obstacle crossing in typically developing children aged 2–5 years (n = 13) and healthy young adults (n = 19) was investigated. The participants were asked to walk along unobstructed and obstructed walkways. The height of the obstacle was set at 10% of the leg length. Gait motion was captured by three RGB cameras. 2D body landmarks were estimated using OpenPose, a marker-less motion capture algorithm, and converted to 3D using direct linear transformation (DLT). Dynamic stability was evaluated using the margin of stability (MoS) in the forward and lateral directions. All the participants successfully crossed the obstacles. Younger children crossed the obstacle more carefully to avoid falls, as evidenced by obviously decreased gait speed just before the obstacle in 2-year-olds and the increased in maximum toe height with younger age. There was no significant difference in the MoS at the instant of heel contact between children and adults during level walking and obstacle crossing in the forward direction, although children increased the step length of the lead leg to a greater extent than the adults to ensure base of support (BoS)-center of mass (CoM) distance. In the lateral direction, children exhibited a greater MoS than adults during level walking [children: 9.5%, adults: 6.5%, median, W = 39.000, p &lt; .001, rank-biserial correlation = −0.684]; however, some children exhibited a smaller MoS during obstacle crossing [lead leg: −5.9% to 3.6% (min–max) for 4 children, 4.7%–6.4% [95% confidence interval (CI)] for adults, p &lt; 0.05; trail leg: 0.1%–4.4% (min–max) for 4 children, 4.7%–6.4% (95% CI) for adults, p &lt; 0.05]]. These results indicate that in early childhood, locomotor adjustment needed to avoid contact with obstacles can be observed, whereas lateral dynamic stability is frangible

Pneumatocele formation in a fatal adult pneumonia patient coinfected with Streptococcus pyogenes emm-type 3 and influenza A: a case report

Background: A pneumatocele is a transient thin-walled lesion and rare complication in adult pneumonia. A variety of infectious pathogens have been reported in children with pneumatoceles. We report the first case of adult pneumonia with pneumatocele formation that is likely caused by Streptococcus pyogenes and coinfection with influenza A virus. Case presentation: A 64-year-old Japanese man presented with a one-week history of fever, sore throat, and arthralgia. He was referred to our university hospital for respiratory distress. He required mechanical ventilation in the intensive care unit (ICU). Bacterial culture detected S. pyogenes in the bronchoscopic aspirates, which was not detected in blood. Although a rapid influenza antigen test was negative, an influenza A polymerase chain reaction (PCR) test was positive. Therefore, he was diagnosed with coinfection of influenza A and group A streptococcus (GAS) pneumonia complicated by probable streptococcal toxic shock syndrome. A chest radiograph on admission showed diffuse patchy opacification and consolidation in the bilateral lung fields. Multiple thin-walled cysts appeared in both middle lung fields on computed tomography (CT). On the following day, the bilateral cysts had turned into a mass-like opacity. The patient died despite intensive care. An autopsy was performed. The pathology investigation revealed multiple hematomas formed by bleeding in pneumatoceles. Conclusions: There have been no previous reports of a pneumatocele complicated by S. pyogenes in an adult patient coinfected with influenza A. Further molecular investigation revealed that the S. pyogenes isolate had the sequence type of emm3

The relationship between the PD-L1 expression of surgically resected and fine-needle aspiration specimens for patients with pancreatic cancer

BACKGROUND: Recently, therapeutic antibodies against programmed death-1/programmed death-ligand 1 (PD-1/PD-L1) have shown promising clinical results for several solid tumors, including pancreatic cancer. In this study, we evaluated the relationship between the PD-L1 expression of surgical resected and fine-needle aspiration (FNA) specimens for patients with pancreatic cancer. METHODS: Of 121 patients who underwent endoscopic ultrasound-guided (EUS)-FNA before surgery for pancreatic cancer in an academic center, the 94 (78%) with adequate FNA specimens for a histological evaluation were retrospectively analyzed. All the patients had undergone upfront surgery without any chemotherapy or radiotherapy. We performed immunohistochemistry (IHC) staining to investigate the PD-L1 expression in both resected and FNA specimens. The positive-stained cells were counted, and their percentage was used for the investigation. RESULTS: Of the 94 patients, 16 (17%) and 11 (10%) were defined as positive on resected cancer specimens using cutoff points of 5% and 10% positively stained cancer cell counts, respectively. The concordance rates for the positive frequency of PD-L1 expression between resected and FNA specimens were 44% (7/16) and 55% (6/11) when the positivity was set to ≥ 5% and ≥ 10%, respectively. The concordance rates for the negative frequency of PD-L1 expression between two specimens were 97% (76/78) and 99% (82/83) when the positivity was set to ≥ 5% and ≥ 10%, respectively. CONCLUSIONS: Approximately, half of the patients with PD-L1 expression positive and almost all the patients with PD-L1 expression negative could be diagnosed on FNA specimens

喫煙は小胞体ストレスを惹起し、RhoAの活性化を介してefferocytosisを抑制する

長崎大学学位論文 [学位記番号]博（医歯薬）甲第1295号 [学位授与年月日]令和2年12月2

Prediction of the prognosis of advanced hepatocellular carcinoma by TERT promoter mutations in circulating tumor DNA

Background and Aim Human telomerase reverse transcriptase (TERT) promoter mutations were the most prevalent mutations in patients with hepatocellular carcinoma (HCC). We tried to detect the mutations with plasma circulating tumor DNA (ctDNA) in patients with advanced HCC and elucidated their clinical utility. Methods Circulating tumor DNA in plasma was extracted from 130 patients with advanced HCC who were treated with systemic chemotherapy (n = 86) or transcatheter arterial chemoembolization (n = 44), and TERT promoter mutations were examined with digital droplet polymerase chain reaction. The correlations between these mutations and the clinical outcome of patients were analyzed. Results Of the 130 patients examined, 71 patients (54.6%) were positive for TERT promoter mutations in ctDNA, of which 64 patients were −124bp G > A and 10 were −146bp G > A. The presence of TERT promoter mutations was correlated with large intrahepatic tumor size (P = 0.05) and high des‐gamma carboxyprothrombin (P = 0.005). Overall survival of the patients with the mutations was significantly shorter than those without them (P Conclusions TERT promoter mutations in ctDNA were associated with short survival and could be a valuable biomarker for predicting the prognosis of patients with advanced HCC

Short-term outcomes of preoperative chemotherapy with docetaxel, oxaliplatin, and S-1 for gastric cancer with extensive lymph node metastasis (JCOG1704)

The version of record of this article, first published in Gastric Cancer, is available online at Publisher’s website: https://doi.org/10.1007/s10120-023-01453-7.Background: The prognosis for marginally resectable gastric cancer with extensive lymph node metastasis (ELM) remains unfavorable, even after R0 resection. To assess the safety and efficacy of preoperative docetaxel, oxaliplatin, and S-1 (DOS), we conducted a multicenter phase II trial. Methods: Eligibility criteria included histologically proven HER2-negative gastric adenocarcinoma with bulky nodal (bulky N) involvement around major branched arteries or para-aortic node (PAN) metastases. Patients received three cycles of docetaxel (40 mg/m², day 1), oxaliplatin (100 mg/m², day 1), and S-1 (80–120 mg/body, days 1–14), followed by gastrectomy with D2 plus PAN dissection. Subsequently, patients underwent postoperative chemotherapy with S-1 for 1 year. The primary endpoint was major (grade ≥ 2a) pathological response rate (pRR) according to the Japanese Classification of Gastric Carcinoma criteria. Results: Between October 2018 and March 2022, 47 patients (bulky N, 20; PAN, 17; both, 10) were enrolled in the trial. One patient was ineligible. Another declined any protocol treatments before initiation. Among the 45 eligible patients who initiated DOS chemotherapy, 44 (98%) completed 3 cycles and 42 (93%) underwent R0 resection. Major pRR and pathological complete response rates among the 46 eligible patients, including the patient who declined treatment, were 57% (26/46) and 24% (11/46), respectively. Common grade 3 or 4 toxicities were neutropenia (24%), anorexia (16%), febrile neutropenia (9%), and diarrhea (9%). No treatment-related deaths occurred. Conclusions: Preoperative chemotherapy with DOS yielded favorable pathological responses with an acceptable toxicity profile. This multimodal approach is highly promising for treating gastric cancer with ELM